Project Summary/Abstract Tuberous Sclerosis Complex (TSC), present in 1/6000 live births, is a neurocutaneous disorder resulting from a spontaneous or autosomal dominantly inherited mutation in either TSC1 or TSC2. TSC is also a leading cause of autism spectrum disorder (ASD) occurring in as many as 50%. Epilepsy in TSC which occurs in 90% has been associated with ASD especially if epilepsy occurs in the first year of life. Speech and language disorders without ASD in TSC are not well- described. Further, there are no clinical biomarkers for ASD in this high-risk population. Clinical trials of neurobiologically targeted medications are ongoing including preventative trials. These trials are currently focused primarily on early treatment/prevention of epilepsy and neurodevelopmental status as a secondary outcome. Future trials could focus primarily on prevention of poor neurodevelopmental outcomes, but clinical biomarkers are needed. The aim of the current research proposal, a first step in preparation for a K23 submission, has been designed to address this gap. The aim of the current Diversity Supplement proposal is to randomly select 60 recordings of infants from the TACERN database (see below) for research on Tuberous Sclerosis Complex (TSC) vocal development. We will analyze and measure possible differences in protophone rates and especially canonical babbling rates of these 60 infants with TSC based on videos obtained at age 12 months using AACT (Action Analysis, Coding, and Training), the coding and analysis system that has been developed in the parent grant setting. These 60 videos have been converted to files appropriate for AACT analysis and stored securely were obtained from a complete TACERN (Tuberous Sclerosis Complex Autism Center of Excellence Network) dataset. TACERN includes 5 sites with TSC clinics, and the dataset is from a multisite, prospective cohort study of 160 children with TSC, ages 0-1 month up to 36 months designed to examine early markers of the development of epilepsy and autism spectrum disorder in babies with TSC. This study included comprehensive psychological, language and autism and videos of language evaluations at 12 and 18 months. The children in the study are currently at least 4 years old. This project will test potentially important hypotheses about TSC and vocal development: 1. Infants with TSC who develop autism spectrum disorder (ASD) are expected to show lower canonical babbling rates than those who do not develop ASD. 2. Infants with TSC who develop ASD are expected to show lower overall volubility rates than those who do not develop ASD. Currently, parents of infants with TSC are aware of the high risk of ASD but are left with a wait and see approach. This project and the subsequent K award application aim to address this issue by studying infant vocal development as an early clinical biomarker of ASD.